Related Experiment Video

Updated: Feb 15, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.1K

Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC by targeting GSTP1

Wei Hang1, Zhi-Xian Yin2, Gang Liu2

  • 1Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Huanhu Hospital, Tianjin, China. hangwei2627@126.com.

Oncogene
|January 20, 2018
PubMed

Insights

Piperlongumine (PL) and APR-246 synergize to selectively kill head and neck squamous cell carcinoma (HNSCC) cells by targeting glutathione S-transferase pi 1 (GSTP1). This combination therapy induces cell death independently of TP53 mutations, offering a new therapeutic strategy for HNSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • TP53 mutations are common in head and neck squamous cell carcinoma (HNSCC), correlating with high recurrence rates.
  • Existing therapies aim to target TP53 mutations or restore wild-type (WT) TP53 activity.
  • PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its analogue APR-246 can reactivate mutant p53 DNA-binding and WT p53 functions.

Purpose of the Study:

  • To investigate the synergistic effect of piperlongumine (PL) and APR-246 in HNSCC treatment.
  • To elucidate the mechanism underlying the selective toxicity of the PL/APR-246 combination.
  • To evaluate the therapeutic potential of PL and APR-246 in preclinical models of HNSCC.

Main Methods:

  • Co-treatment of HNSCC cells with piperlongumine (PL) and APR-246.
  • Assessment of cell death (apoptosis and autophagic cell death) in cancer cells and normal cells.
  • Investigation of TP53 mutation status and glutathione S-transferase pi 1 (GSTP1) expression.
  • Measurement of reactive oxygen species (ROS), glutathione (GSH), and glutathione disulfide (GSSG) levels.
  • Xenograft tumor growth inhibition studies in SCID mice.

Main Results:

  • PL and APR-246 synergistically induce apoptosis and autophagic cell death selectively in HNSCC cells, sparing normal cells.
  • The sensitization of HNSCC cells to APR-246 by PL is independent of TP53 mutations.
  • The combination treatment suppresses GSTP1 activity, leading to ROS accumulation, GSH depletion, GSSG elevation, and DNA damage.
  • Ectopic GSTP1 expression or N-acetyl-L-cysteine (NAC) pre-treatment abrogates ROS elevation and reduces treatment-induced cell death and DNA damage.
  • PL and APR-246 administration inhibits UMSCC10A xenograft tumor growth in vivo.

Conclusions:

  • HNSCC cells exhibit selective sensitivity to the combination of PL and APR-246.
  • The synergistic effect is mediated by the suppression of GSTP1, leading to ROS induction.
  • This combination represents a promising therapeutic strategy for HNSCC, irrespective of TP53 mutation status.

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.8K
Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria08:22

Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria

Published on: May 16, 2025

600

Related Concept Videos

Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.6K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
10.3K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
16.4K
Cross-reactivity00:42

Cross-reactivity

Overview
33.2K
Reactivity of Enols01:18

Reactivity of Enols

Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is...
4.2K
What is Natural Selection?01:32

What is Natural Selection?

Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
129.9K